1. Field of the Invention
The present invention relates to methods and therapeutic combinations for treating and preventing demyelination in a subject comprising the administration of sterol absorption inhibitor(s).
2. Description
Nerve fibers are wrapped with many layers of insulation known as the myelin sheath. Like insulation around an electrical wire, the myelin sheath permits electrical impulses to be conducted along the nerve fiber with speed and accuracy. When normal development of the myelin is impaired (for example in subjects having Tay-Sachs disease, Niemann-Pick disease, Gaucher's disease and Hurler's syndrome), permanent, extensive neurological defects can result. Also, the myelin sheath can be damaged by stroke, inflammation, immune diseases, metabolic disorders, poison or drugs. If the sheath is able to regenerate itself, normal nerve function can be partially or fully restored. If demyelination is extensive, the underlying nerve can die and cause irreversible damage. Demyelination in the central nervous system (brain and spinal cord) occurs in several primary demyelinating diseases, such as multiple sclerosis, acute disseminated encephalomyelitis, adrenoleukodystrophy, adrenomyeloneuropathy, Leber's hereditary optic atrophy and HTLV-associated myelopathy.
Multiple sclerosis (“MS”) is characterized by the loss of patches of myelin in the nerves of the eye, brain and/or spinal cord. It is believed that the body produces antibodies against its own myelin that provoke inflammation and damage the myelin sheath. Heredity and environment appear to play some role in the disease, although it is believed that a virus or unknown antigen somehow triggers the autoimmune process. Symptoms depend upon the area affected. Demyelination in nerve pathways that bring signals to muscles can produce problems with movement (motor symptoms), such as weakness, clumsiness, difficulty in walking or maintaining balance, tremor, double vision, problems with bladder or bowel control, stiffness, unsteadiness or unusual tiredness. Demyelination in nerve pathways that bring signals to the brain can cause sensory symptoms, such as numbness, tingling, dysesthesias, visual disturbances, sexual dysfunction, dizziness or vertigo. Magnetic resonance imaging (MRI) can reveal areas of the brain that have lost myelin, and may even distinguish areas of recent demyelination from areas that occurred some time ago.
Treatments for multiple sclerosis include injection with beta-interferon, which can decrease the frequency and occurrence of flare-ups and slow the progression to disability; injection with glatiramer acetate, which can reduce the frequency of relapses; or administration of corticosteroids, such as prednisone, to relieve acute symptoms. Recently, statins such as simvastatin and atorvastatin (HMG CoA reductase inhibitors) have been studied for their immunomodulatory effects in treating MS. C. Pelfrey, “ACTRIMS-ECTRIMS 2002 (Part II)”, IDDB Meeting Report, Sep. 18-21, 2002 Baltimore, Md., USA, (Oct. 3, 2002).
There is a need in the art for improved compositions and treatments for demyelination and associated diseases such as multiple sclerosis.